The objective is to satisfy an important need, the need to know the biochemical nature of the different kinds of cells in muscle and nervous system. Brain function depends on the interplay of diverse kinds of cells, grandly entangled. The admixture of the many cell types and the fact that the functional state differs from cell to cell, and from moment to moment, means that the macroscopic approaches are limited in their usefulness. Muscle is an intimate mixture of cells that differ greatly in chemical composition. Muscle fibers lying next to each other may vary as much as 50-fold in the ratios between particular enzymes, ant the differences can be exaggerated in muscle disease. Therefore, here also macroscopic studies are inadequate. To attack this situation, an analytical methodology is available which has virtually unlimited sensitivity and which makes it possible to measure nearly any enzyme or metabolite in single nerve cell bodies, in nuclei of large neurons, in other neuronal structures of similar size, and in small pieces of individual muscle fibers. The purpose of the project is to exploit this analytical capability to the study of muscle and the central nervous system. In some cases, single neurons or portions thereof will be examined. In other cases, small groups of cells will be studied. In the case of muscle, the technique is such that the same individual fibers can be analyzed for a great many enzymes, metabolites and cofactors. The brain projects for some time will be focused on in vitro incubation of slices from hippocampus and cerebellum. Emphasis will be on assessing regional metabolic patterns of the effects of hypoxia, hypoglycemia, hyperglycemia and heat stroke, and recovery from each of these insults. Obviously, these studies are related to human health problems. Some of the muscle projects will consist of more extensive studies of metabolite responses to continuous low intensity stimulation for periods ranging from 2 minutes to 24 hours. These studies may contribute to a better understanding of the consequences of prolonged moderate exercise. A continue collaboration with Dr. John Lawrence is planned to study signal transduction pathways involved in the hormonal control of metabolism.